Animal feeds, animal feed supplements, and methods



maze- -whereinX represents a monovalent radical the group consisting of lower alkyl, lowerjalkoxy and I halogen; Zrepresentsa monovalent radicalselected from i United States Patent i 4 2,941,884 ANIMAL FEEDS, ANIMAL FEED SUPPLEMENTS,

- AND METHODS John Alfred Aeschlimann and Benjamin Tabenkin, Montclair, NJ., assignors to Holfmann-La Roche Inc., Nutley, N-IL, a corporation of New Jersey No Drawing. Filed Oct. 9, 1957, Ser. No. 689,059

v 9 Claims. (Cl. 992) This invention-relates to new and useful improvements in feeds for animals and in methods of feeding animals. More particularly, the invention relates to animal feed compositions containing a hypoglycemic sulfonylurea; to feed supplements containing a hypoglycemic sulfonylurea, which can be admixed with conventional animal feeds or conventional basal rations for animals or nutrients or other diluent materials suitable for oral ingestion by animals, such feed supplements thus being useful also to prepare the animal feed compositions of the invention; andto improved methods of growing animals by feeding them the animal feed compositions or feed supplements of the invention.

'By'hypoglycemic sulfonylurea is meant a compound containing a sulfonylurea linkage the art; general methods being taught, for instance, in

the following German patent applications which have been laid open to the public for inspection:

Serial No. Filed Opened Fl8l3fi IVh/12o, 17/03 8- 8-55 9-27-56 ,Fl8339 IVb/l20, 17/03.- 9- 3-55 l22756 F18648 IVb/l20, l7/03 10-14-55 12-13-56 Fl8659 IVb/120, 17/03.. 10-15-55 12-27-56 Fl9253 IVb/l20, 17/03 l- 756 3 7-67 B38071 IVb/l20, 17/03 (German "Auslegeschrlit Among the preferred hypoglycemic sulfonylureas are hypoglycemic phenylsulfonylureas having' the formula H 0 ia aa-i-i-iselected from the-group consisting of monovalent secondary and tertiary organic amino radicals, and n represents' a small natural number. 7

Patented June 21, 1960 ice . -ethylmercapto-n-propylamino, neobornylamino, and the Illustrative meanings of the symbol X in the ;above formula are: methyl, ethyl, isopropyl, methoxy, chlorine, bromine, and the like. Illustrative values of the symbol n in'the above formula are: 0, 1 and 2. lllustrative meanings of the symbol Z .in the above formula are: ethylamino,-isopropylamino, n-butylamino, 2,2-dimethylpropylamino, 'n-hex'ylamino, 4-heptylamino, l-octylamino,

allylamino, crotylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino, p-methylcyclohexylamino, cy-

.1clohexylmethylamino, a -cyclohexenylamino, methoxypro- -.pylamino, n-propoxypropylamino, p-ethoxyethylamino,

hke. v

The following are exemplary of phenylsulfonylureas that can be employed in the practice of the invention:

1-n-buty1-3-phenylsulfonylurea I 1-n-butyl-3-p-tolylsulfonylurea 1-tert.-butyl-3-p-tolylsulfonylurea 1-n-heXyl-3-m-methoxyphenylsulfonylurea 1-n-propyl-3-p-isopropylphenylsulfonylurea l-n-hexyl-3-m-tolylsulfonylurea 1-allyl-3-p-tolylsulfonylurea l-isoamyl-3-p tolylsulfonylurea 1-cyclohexyl-3-p-tolylsulfonylurea I 1-cylohexyl-3-p-ethylphenylsulfonylurea l-n-butyl-3-m-chlorophenylsulfonylurea l-n-butyl-3-p-bromophenylsulfonylurea 1-cyclohexy1 3-p-chlorophenylsulfonylurea l-isobutyl-3-(3-ehloro4-methylphenylsulfonyl)urea -1-cyclohexyl-3-(2,4 dimethylphenylsulfonyl)urea 1-isobutyl-3-(3,4-dimethoxyphenylsulfonyl)urea 1- (3 -ethoxy-n-propyl) -3 -p-tolylsulfonylurea l-tetrahydrofurfuryl-3-p-tolylsulfonylurea l-fl-isopropoxyethyl-3-p-tolylsulfonylurea 1-ot-pyridyl-3 -p-tolylsulfonylurea I l-(4-methyl-2-pyridyl)-3-p-tolylsulfonylurea 1-( S-methylmercapto-n-propyl) -3 -p-tolylsulfonylure 'l-isopropoxyethyl-3-phenylsulfonylurea.

Each'of the above listed compounds is specifically disclosed in the published Germanpatent applications previously listed herein. f

Additional examples of hypoglycemic sulfonylureas which can be employed in practicing the invention are:

1-d-( -bornyl-3 -phenyl sulfonylurea l-d( .l. -bornyl-3 -p-tolylsulfonylurea 1-d-( -ne0bornyl-3 -p -tolylsulfonylurea 1-fenchyl-3-phenylsulfonylurea Each of the above listed compounds is specifically disclosed in'a copending'application of John Alfred Acschlimann and Arthur Stempel, Serial No. 687,373, filed Octo her 1, 1957, entitled Substituted Ureas. Whereas numerous examples of hypoglycemic sulfonylureas, useful in practicing the' 'present invention,

have been referred to above, it should be understood that no hypoglycemic sulfonylurea isclaimed herein as a novel compound, nor is the preparation of anyhypoglycemic sulfonylurea claimed herein as a novel'm'ethod.- ;-j

The animal feed compositions of the invention can be made' by mixing a hypoglycemic sulfonylurea compound with conventional ingredients of animal feeds. Theimixing-can be accomplished by methods known'per se. A convenient method of making the improved animal feeds of the invention comprises charging conventional feed ingredients and a hypoglycemic sulfonylur'ea to a batch mixer and operating the mixer until the contents thereof are uniformly dispersed to give a mixture which is homogeneous throughout; An alternative method of preparing animal-feedsaccording to the invention comprises adding a hypoglycemic sulfonylurea feed supplement to a conventional animal feed. 5 Thus, it will often be convenient to premix the hypoglycemic sulfonylureacompoundwith a diluent which is suitable for oral ingestion by the animal (this diluent may itself be a nutrient material for the animal) and-subsequently to mix the premixedsupplement so obtained with a commercially 'obtainableconproved animal feed compositions of the invention. As

another alternative, a hypoglycemic sulfonylurea compound may be intimately admixed with sucha material as corn mealor soy bean oilfmeal to give a uniformly blended composition, and the hypoglycemic sulfonylurea feed supplement composition so obtained may be subseguently mixed with additional nutrient ingredients-suitable to make a finished improved feed according to the invention. Preferably, the hypoglycemic sulfonylurea compound is employed in an amount that will give a finished animal feed having a proportion of from about 0.001% to about 0.1%, by weight, of hypoglycemic sulfonylurea compound; but it will be understood that the invention embraces the use of any proportion of hypoglycemic sulfonylurea compound that will give beneficial and economically desirable results in the utilization by the animal of its feed. An especially preferred proportion of hypoglycemic sulfonylurea compound in the feed is from about 0.005% to about 0.05% by weight.

The novel methods of the invention, whereby a hypoglycemic sulfonylurea compound is made a part of the animals diet, can be practiced by feeding growing animals on complete animal feed rations, improved by incorporation of a hypoglycemic sulfonylurea therein according to the present invention. Alternatively, it may be desirable in some cases to feed the animal a hypoglycemic sulfonylureau feed composition which contains less nutrient material than is found in the animals total diet. For example, the animal can be fed alternately on conventional rations and on hypoglycemic sulfonylurea feed compositions of the invention. Or, the hypoglycemic sulfonylurea compound can be dissolved in the animal s drinking water and can be furnished to the animal in this way.

Preferred aspects of the'invention relate to swine feed compositions comprising swine nutrients and hypoglycemic sulfonylureas, and to methods of growing swine by feeding them such compositions. It has been found that swine grown on animal feed compositions comprising conventional rations and, in addition, a hypoglycemic compound consume feed with greater etficiency. That is to say, it takes less feed, when employing the swine feed compositions of the present invention, to procure a desired gain in weight of the swine thanwhen employing conventional swine feed compositions. Additionally, it has been observed that swine grown on hypoglycemic sulfonylurea feed compositions of the invention, when butchered, have leaner carcasses than when grown on conventional feed compositions, and the carcasses contain a greater percentage of primal cuts.

4 Weight (lbs.) Vitamin A and D feedingoil (containing per pound 1,020,000 U.S.P. vitamin A units and 136,000 U.S.P. units of-vitarnin D) 6 D-activated animal sterol (containing per pound- 1,360,000 U.S.P. vitamin D units) Total (approx. protein, 3.5%fat, 5% fiber) --3000.0

(B) 5 g. of l-n-butyl-3-p-tolylsulfonylureawas mixed 7 with 500 g. of the chick starter mash described in Example The following examples are illustrative, but not limitative,-of the invention.

7 Example I i (A) A basal chick starter'mash was made bymixing the following ingredients;

Weight (lbs) Wheat middlings 400 Yellow corn meal 1268.5 Fine ground oats H 200 Alfalfa meal 100 Soy bean oil meal 400 Meat scraps 200 Fish meal 90 Dried corn distillerssolubles a 120 Dried whey a I100 Dried skim milk 30 Riboflavin supplement (containing per pound 227 .mg. of riboflavin) l2 1 Ground limestone 30 Dicalcium phosphate 1 30 Iodizedsalt 10 Trace minerals 1 1.5

1 Content, in p.p.m. per tenet feed:

Manganes a 1 65.00

.Coba 0.75

Copper 1.5'0 Iodine 1.50 Iron 30.00 {Zinc V 1 l 1.30

MA) above, until a uniformly blended mixture was obtained. The entire amount of this premixed feed supplement was then uniformly blended with 4500 g... of the same chick starter mash.

(C) 0.5 g. of l'-tert.-butyl- 3-phenylsulfonylurea was mixed with 50 g. of yellow corn meal until a uniformly blended mixture was obtained. The supplement so obtained was then mixed with 5000 g. of the chick starter mash described in Example 1(A) above until a uniformly blended mixture was obtained.

(D) One-fourth pound of l-n butyl-3-phenylsulfonylurea was premixed with one pound of soy bean oil meal until a uniformly blended mixture was obtained. 'The premixed supplement thus prepared was then mixed with 500 pounds of the chick starter mash described in EX- ample 1(A) above, until a uniformly blended mixture was obtained.

" Weight (lbs.') Corn 325.0

Soy bean oil meal 60.5 Meatscraps 22.0 Alfalfa hay; -i 250 Salt 2.5 Antibiotic feed supplement (containing per pound pound 3.6 g. of chlortctracycline) 2.5 Glucose 60:5 Dicalcium phosphate L 2.0 B vitamin feed supplement (containing per pound 2 g. of riboflavin, 4 'g. of pantothenic acid, 9 g.

of niacin, 10 g. of choline chloride and '60 mg.

of folic acid) 0.25 Dry vitamin A (containing per pound 9,080,000

U.S.P. vitamin A units) 0.1 D-activated animal sterol (containing per pound 1,360,000 U.S.P; vitamin D units) j 1.5

Total (approx. 14% protein) 501.85

"ingredientslisted in Example 2(A) above, in the quantities there listed. a

- I 0) A second' hypoglycemic sulfonylurea swine feed was madebyblending' togetheruniformly 25 g. of lcyclohexyl-3-p-tolylsulfonylurea andall of "the ingredients pigs, and the secondand third groups-each'containing pigs. Thepigs in group 1 were fed on the ration described'in Example 2'(A). Those in group 2 were fed '"on the ration described in Example 2(B).. Those in group 3. were fed on the rat iondescribed in 'Example 2(6). "The pigs were slaughtered as theyreached market weight, approximately 200 pounds. The following table lists the significant observations:

Group Group Group 1 2 3 N0. pigs 5 6 6 Slaughter weight (lbs.) 205. 6 203. 7 209. 2 Daily gain (lbs.) 1.53 1. 56 1 53 Feed per cwt. gain (lbs 401v 4 353. 3 379. 4 Warm dressing percent 82. 78 81. 60 81.60 Carcass length (cm.) 73. 8 74. 75. 4 Leg length (cm) 50v 9 51. 51. 7 Earn length (cm.) 34. 7 35. 4 35. 5 Carcass depth (cm.) 35.7 35. 3 35. 8 Carcass thickness (cm.) 27.4 27.0 27. 3 Mean backfat thickness (in. 1. 58 1. 41 1. 49 Percent primal cuts of live wt 47. 47 48. 48 47. 9.3 Area of loin eye (sq. in.) 4. 26 3. 88 3. 94

l Primal cutsham, loin, Boston butt, picnic, and bacon side.

We claim:

1. An animal feed composition comprising nutrient material for the animal and a hypoglycemic l-substituted- 3-arylsulfonylurea compound.

2. A method of promoting leanness of carcass in swine which comprises feeding growing swine a composition defined by claim 1.

3. A method of improving the utilization of feed by animals which comprises feeding a hypoglycemic l-substituted-3-arylsulfonylurea compound to the animals.

4. An animal feed comprising nutrient material and a hypoglycemic phenylsulfonylurea having the formula wherein X represents a monovalent radical selected from the group consisting of lower alkyl, lower alkoxy and halogen, Z represents a monovalent radical selected from the group consisting of monovalent secondary and tertiary organic amino radicals, and n represents a small natural number.

5. A supplement for admixture with an animal feed comprising a diluent material suitable for oral ingestion by the animal and, admixed therewith, a hypoglycemic phenylsulfonylurea having the formula defined in claim 4.

6. A swine feed comprising a basal ration for swine and a hypoglycemic phenylsul-fonylurea having the formula defined in claim 4.

7. A method of increasing feed efliciency which comprises feeding swine at least in part with a feed defined by claim 6. r

8. An improvement in the preparation of a feed for swine which comprises mixing a hypoglycemic l-substituted-B-arylsulfonylurea compound with a material which is nutrient for swine.

9. An animal feed comprising nutrient material and a hypoglycemic phenylsulfonylurea having the formula 0 (X)nOGH(5-n) I I E-Z wherein X represents a monovalent radical selected from the group consisting of lower alkyl, lower alkoxy and halogen, Z represents a monovalent radical selected from the group consisting of monovalent secondary and ter tiary organic amino radicals, and n represents a small natural number, said hypoglycemic phenylsulfonylurea being present in a proportion of from about 0.001% to about 0.1% by weight of said animal feed.

References Cited in the file of this patent UNITED STATES PATENTS 2,742,362 Aeschlimann et al. Apr. 17, 1956 OTHER REFERENCES Merck Index, 6th Ed. (1952), Rahway, N.J., page 920.

J. A. Ph. A., Practical Pharmacy Ed. 17, September 1956, page 610.

J.A.M.A. March 1956, page 1089. 

1. AN ANIMAL FEED COMPOSITION COMPRISING NUTRIENT MATERIAL FOR THE ANIMAL AND A HYPOGLYCEMIC 1-SUBSTITUTED3-ARYLSULFONYLUREA COMPOUND. 